Conventional and novel impacts of ferric citrate on iron deficiency anemia and phosphorus metabolism in rats

Abstract

Ferric citrate is an oral iron-based phosphate binder, being known to affect iron status and improve iron deficiency anemia (IDA) in chronic kidney disease (CKD) patients. We examined whether oral administration of ferric citrate could change iron status and improve anemia without affecting phosphorus metabolism in iron deficiency anemia rats. In Normal rat study, normal rats were fed a diet containing 0.3 or 3% ferric citrate for 11 days for setting the dose and administration period of ferric citrate. The effects of ferric citrate on iron status-and phosphorus metabolism-related parameters were evaluated using blood and urine samples. Next, an iron deficiency anemia was induced by feeding iron-depleted diet in rats. After 7 days of starting the iron-depleted diet, 0.3% ferric citrate was administered for 7 days by dietary admixture. Iron status-and phosphorus metabolism-related parameters were evaluated with blood and urine samples. In Normal rat study, 3% ferric citrate treatment increased serum iron level and transferrin saturation (TSAT), and decreased serum phosphorus level, intact fibroblast growth factor 23 (iFGF23) level, and urinary phosphorus excretion, but 0.3% ferric citrate treatment showed no effects. On the other hand, in Iron deficiency anemia rat study, 0.3% ferric citrate treatment increased iron status-related parameters and improved anemia, but did not show any apparent changes in phosphorus metabolism-related parameters. In conclusion, ferric citrate could have hematopoietic effects without affecting phosphorus metabolism, and could be a potential option for the treatment of IDA in patients without CKD.

Efficacy and safety of ferric citrate hydrate compared with sodium ferrous citrate in Japanese patients with iron deficiency anemia: a randomized, double-blind, phase 3 non-inferiority study

“…The FC treatment dosage in this study was 500 mg once or twice daily, which is lower than the approved dosage (500–2000 mg three times daily) to treat hyperphosphatemia in patients with CKD in Japan. Furthermore, in other research, high-dose FC treatment decreased the serum phosphorus concentration; whereas, low-dose FC treatment had no effects on the phosphorus concentration in healthy rats with normal renal function [ 21 , 22 ]. Non-clinical studies have also shown that low-dose FC treatment does not significantly change the concentrations of intact fibrosis growth factor 23 (iFGF23) and intact parathyroid hormone (iPTH), which play important roles in the metabolism of phosphorus, in healthy rats [ 21 , 22 ].…”

“…Furthermore, in other research, high-dose FC treatment decreased the serum phosphorus concentration; whereas, low-dose FC treatment had no effects on the phosphorus concentration in healthy rats with normal renal function [ 21 , 22 ]. Non-clinical studies have also shown that low-dose FC treatment does not significantly change the concentrations of intact fibrosis growth factor 23 (iFGF23) and intact parathyroid hormone (iPTH), which play important roles in the metabolism of phosphorus, in healthy rats [ 21 , 22 ]. Taking these results into consideration, we suggest that FC at 500 or 1000 mg/day will not adversely affect phosphorus metabolism during treatment in patients with IDA who have normal kidney function.…”

Ferric citrate for the treatment of hyperphosphatemia and iron deficiency anaemia in patients with NDD-CKD: a systematic review and meta-analysis

“…Notably, recent research on phosphorus homeostasis molecular processes shows a link between hyperphosphatemia and iron insufficiency via the regulating hormone iFGF23. In NDD-CKD patients, ferric citrate taken with meals lowered iFGF23 while increasing iron parameters ( Iida et al, 2020 ). Although the current investigation found that iron citrate had no effect on iFGF23, its efficacy in treating iron deficiency and reducing blood phosphorus levels in NDD-CKD patients is undeniable.…”

Iron-based phosphorus chelator: Risk of iron deposition and action on bone metabolism in uremic rats

“…23 The risk of Fe overload, and its consequent bone deposition should be considered in patients with CKD, given their high frequency of use for the treatment of anemia secondary to CKD, 24 especially when using compounds that facilitate intestinal Fe absorption, such as ferric citrate. 25,26 The phosphorus chelator CH-FeCl is a polymer of chitosan and iron in the ferric form (FeIII). This complex demonstrates a chelating effect without causing Fe deposition in the tissues when administered orally at low doses to rats with normal renal function and diabetes mellitus.…”